new england

The
journal of medicine
established in 1812 January 2, 2014 vol. 370 no. 1

Stenting and Medical Therapy

for Atherosclerotic Renal-Artery Stenosis
ChristopherJ.Cooper,M.D., TimothyP.Murphy,M.D., DonaldE.Cutlip,M.D., KennethJamerson,M.D.,
WilliamHenrich,M.D., DianeM.Reid,M.D., DavidJ.Cohen,M.D., AlanH.Matsumoto,M.D.,
MichaelSteffes,M.D., MichaelR.Jaff,D.O., MartinR.Prince,M.D., Ph.D., EldrinF.Lewis,M.D.,
KatherineR.Tuttle,M.D., JosephI.Shapiro,M.D., M.P.H., JohnH.Rundback,M.D., JosephM.Massaro,Ph.D.,
RalphB.DAgostino,Sr.,Ph.D., and LanceD.Dworkin,M.D., for the CORAL Investigators*

a bs t r ac t

BACKGROUND From the University of Toledo, Toledo, OH

(C.J.C.); Rhode Island Hospital (T.P.M.,
Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two L.D.D.) and Alpert Medical School of
randomized trials that did not show a benefit of renal-artery stenting with respect to Brown University (T.P.M., L.D.D.) both
in Providence; Harvard Clinical Research
kidney function, the usefulness of stenting for the prevention of major adverse renal Institute (D.E.C., J.M.M., R.B.D.), Beth Is-
and cardiovascular events is uncertain. rael Deaconess Medical Center (D.E.C.),
Massachusetts General Hospital (M.R.J.),
METHODS Brigham and Womens Hospital (E.F.L.),
and Boston University School of Public
We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis Health (R.B.D.) all in Boston; University
and either systolic hypertension while taking two or more antihypertensive drugs or of Michigan, Ann Arbor (K.J.); University of
chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy Texas Health Science Center, San Antonio
(W.H.); National Heart, Lung and Blood
alone. Participants were followed for the occurrence of adverse cardiovascular and renal Institute, Bethesda, MD (D.M.R.); Saint
events (a composite end point of death from cardiovascular or renal causes, myocar- Lukes Mid America Heart Institute, Uni-
dial infarction, stroke, hospitalization for congestive heart failure, progressive renal versity of MissouriKansas City School of
Medicine, Kansas City (D.J.C.); University
insufficiency, or the need for renal-replacement therapy). of Virginia, Charlottesville (A.H.M.); Uni-
versity of Minnesota, Minneapolis (M.S.);
RESULTS Weill Cornell Medical Center, New York
Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the (M.R.P.); Providence Sacred Heart Medical
Center and University of Washington
primary composite end point did not differ significantly between participants who under- School of Medicine, Spokane (K.R.T.); Mar-
went stenting in addition to receiving medical therapy and those who received medical shall University, Huntington, WV (J.I.S.);
therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confi- and Holy Name Medical Center, Teaneck
NJ (J.H.R.). Address reprint requests to Dr.
dence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between Cooper at the Department of Medicine,
the treatment groups in the rates of the individual components of the primary end point or University of Toledo, 3000 Arlington Ave.,
in all-cause mortality. During follow-up, there was a consistent modest difference in sys- MS 1036, Toledo, OH 43614, or at
christopher.cooper@utoledo.edu.
tolic blood pressure favoring the stent group (2.3 mm Hg; 95% CI, 4.4 to 0.2; P=0.03).
*A complete list of the investigators in
CONCLUSIONS the Cardiovascular Outcomes in Renal
Atherosclerotic Lesions (CORAL) study
Renal-artery stenting did not confer a significant benefit with respect to the preven- is provided in the Supplementary Ap-
tion of clinical events when added to comprehensive, multifactorial medical therapy pendix, available at NEJM.org.
in people with atherosclerotic renal-artery stenosis and hypertension or chronic kid- This article was published on November
18, 2013, at NEJM.org.
ney disease. (Funded by the National Heart, Lung and Blood Institute and others;
N Engl J Med 2014;370:13-22.
ClinicalTrials.gov number, NCT00081731.)
DOI: 10.1056/NEJMoa1310753
Copyright 2013 Massachusetts Medical Society.

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 The n e w e ng l a n d j o u r na l
R
enal-artery stenosis, which is
present in 1 to 5% of people with hyper-
tension,1,2 often occurs in combination
with peripheral arterial or coronary artery dis-
ease.3,4 Results of community-based screening
suggest that the prevalence among persons older
than 65 years of age may be as high as 7%.5
Renal-artery stenosis may result in hypertension,
ischemic nephropathy, and multiple long-term
complications.6 Uncontrolled studies performed
in the 1990s suggested that renal-artery angio-
plasty or stenting resulted in significant reduc-
tions in systolic blood pressure7,8 and in the
stabilization of chronic kidney disease.9,10 Sub-
sequently, there were rapid increases in the rate
of renal-artery stenting among Medicare benefi-
ciaries, with the annual number of procedures
increasing 364% between 1996 and 2000.11
However, three randomized trials of renal-artery
angioplasty failed to show a benefit with respect
to blood pressure.12-14 Two subsequent random-
ized trials of stenting did not show a benefit
with respect to kidney function.15,16 To our
knowledge, no studies to date have been de-
signed specifically to assess clinical outcomes.
Given the prevalence of atherosclerotic renal-
artery stenosis, this condition is an important
public health issue. If stenting prevents the pro-
gression of chronic kidney disease and lowers
blood pressure, it has the potential to prevent
serious health consequences, including adverse
cardiovascular and renal events. In contrast, if
stenting confers neither of these benefits, it is
likely to incur substantial cost without a public
health advantage. Therefore, we performed a
randomized clinical trial to determine the ef-
fects of renal-artery stenting on the incidence of
important cardiovascular and renal adverse
events.17
Me thods
Study Oversight
The Cardiovascular Outcomes in Renal Athero-
sclerotic Lesions (CORAL) study was a multi-
center, open-label, randomized, controlled trial
that compared medical therapy alone with med-
ical therapy plus renal-artery stenting in patients
with atherosclerotic renal-artery stenosis and
elevated blood pressure, chronic kidney disease,
or both. The methods have been described previ-
ously.17 The trial protocol was developed by the
steering committee (see the Supplementary Ap-
14 n engl j med 370;1nejm.org January 2, 2014
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of m e dic i n e
pendix, available with the full text of this article
at NEJM.org) and was approved by the institu-
tional review board at each participating center.
The members of the steering committee vouch
for the accuracy and completeness of the data and
analyses and for the fidelity of this report to the
trial protocol, which is available at NEJM.org.
Funding was provided by the National Heart,
Lung, and Blood Institute. Medications were
donated by AstraZeneca and Pfizer. The short-tip
Angioguard device was donated by Cordis, and
supplemental financial support was provided by
both Cordis and Pfizer. None of the funders had
any role in the design of the trial protocol, in the
collection, analysis or interpretation of the data,
or in the decision to submit the manuscript for
publication. The trial was conducted under the
guidance of an independent data and safety
monitoring board convened by the National
Heart, Lung, and Blood Institute.
Study Population
Before entry into the trial, all participating sites
were required to qualify in a roll-in phase.
Qualification involved approval of the expertise
of the lead onsite interventionalist by the angio-
graphic core laboratory. The details of this ap-
proval process are described in the Supplemen-
tary Appendix.
Trial enrollment began on May 16, 2005. All
participating patients provided written informed
consent. According to the original trial protocol,
persons with severe renal-artery stenosis were
eligible if they had hypertension with a systolic
blood pressure of 155 mm Hg or higher while
receiving two or more antihypertensive medica-
tions. Severe renal-artery stenosis was defined
angiographically as stenosis of at least 80% but
less than 100% of the diameter or stenosis of at
least 60% but less than 80% of the diameter of
an artery, with a systolic pressure gradient of at
least 20 mm Hg. All angiograms were analyzed
by the angiographic core laboratory at the Uni-
versity of Virginia with the use of a validated
computerized quantitative vascular analysis pro-
gram (Medis QVA 6.0).
A number of subsequent changes were made
in the enrollment criteria during the course of the
trial but before the trial concluded or the data
were unblinded. The threshold of 155 mm Hg for
defining systolic hypertension was no longer
specified. Patients who did not have systolic
hypertension but who had renal-artery stenosis
 Stenting and Medical Ther apy for Renal-Artery Stenosis
could be enrolled if they had chronic kidney
disease, which was defined as an estimated glo-
merular filtration rate (GFR) of less than 60 ml/
min/1.73 m2 of body-surface area, as calculated
with the use of the modified Modification of
Diet in Renal Disease (MDRD) formula.18 Severe
renal-artery stenosis could be identified with the
use of duplex ultrasonography, magnetic reso-
nance angiography, or computed tomographic
angiography.
Exclusion criteria were renal-artery stenosis
due to fibromuscular dysplasia, chronic kidney
disease from a cause other than ischemic ne-
phropathy or associated with a serum creatinine
level higher than 4.0 mg per deciliter (354 mol
per liter), kidney length of less than 7 cm, and a
lesion that could not be treated with the use of
a single stent. Complete inclusion and exclusion
criteria are listed in the Supplementary Appendix.
Randomization and Interventions
We assigned participants, in a 1:1 ratio, to either
medical therapy alone or stenting plus medical
therapy. Randomization was performed by means
of an interactive voice randomization system
with the use of a permuted block design. All
participants in both treatment groups received
antiplatelet therapy and other protocol-driven
medical therapies to control blood pressure and
glucose and lipid levels in accordance with
guidelines.19,20
Unless otherwise contraindicated, the follow-
ing medications were mandated by the protocol:
the angiotensin II type-1 receptor blocker cande-
sartan (Atacand, AstraZeneca), with or without
hydrochlorothiazide, and the combination agent
amlodipineatorvastatin (Caduet, Pfizer), with
the dose adjusted on the basis of blood pressure
and lipid status. Participants received voucher
cards that allowed them to obtain the medica-
tions (candesartan, hydrochlorothiazide, and
atorvastatinamlodipine) from their local phar-
macies at no personal cost. The target blood
pressure was less than 140/90 mm Hg in patients
without coexisting conditions and less than
130/80 mm Hg in patients with diabetes or
chronic kidney disease. Medications were adjusted
until the blood-pressure goal was reached.17
Blood pressure was measured three times, 2 min-
utes apart, in each participant, with the use of
an oscillometric device. The measurements were
made while participants were sitting quietly, and
the mean of the last two measurements was used.
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Participants in the stent group underwent
placement of a Palmaz Genesis stent (Cordis);
predilation was performed at the discretion of
the investigator. All renal arteries with stenoses
of 60% or more were treated. In patients with
multiple stenoses, stenting could be performed
as a single procedure or in intervals of 2 to 4 weeks.
Before August 2006, the use of the short-tip An-
gioguard device was required for embolic protec-
tion; after this date, an embolic protection device
approved by the Food and Drug Administration
(FDA) was used at the operators discretion.
Crossovers from the medical therapy group to
the stent group were reviewed by a designated
crossover committee. Crossovers were not ap-
proved unless a qualifying outcome event had
occurred or all of the following conditions were
met: acute anuric renal failure, complete occlu-
sion of all renal arteries, and at least one kidney
more than 8 cm in length.
Study End Points
The primary end point was the occurrence of a
major cardiovascular or renal event a compos-
ite of death from cardiovascular or renal causes,
stroke, myocardial infarction, hospitalization for
congestive heart failure, progressive renal insuf-
ficiency, or the need for permanent renal-replace-
ment therapy. Myocardial infarction was adjudi-
cated on the basis of the presence of clinical
symptoms or electrocardiographic changes and
elevated cardiac markers. Hospitalization for con-
gestive heart failure was included in the analysis
if the patient was hospitalized for 12 hours or
longer because of documented signs and symp-
toms of heart failure and received intravenous
therapy (vasodilators, diuretics, or inotropes) dur-
ing the hospital stay. Progressive renal insuffi-
ciency was defined as a reduction from baseline
of 30% or more in the estimated GFR, with the
reduction sustained for 60 days or longer and not
attributable to other causes. Secondary clinical
end points included the individual components
of the primary end point (with death from car-
diovascular causes and death from renal causes
as separate end points), as well as all-cause mor-
tality. Complete definitions of the study end
points are provided in the Supplementary Appen-
dix. A single end-point committee whose members
were unaware of the group assignments adjudi-
cated all end points.
The definitions of end points were modified
on March 12, 2012, by the CORAL steering com-
15
 The n e w e ng l a n d j o u r na l of m e dic i n e

mittee, and the modifications were approved by
the data and safety monitoring board and the
FDA. These modifications, which were made
before the data were unblinded and with the
steering committee unaware of event rates in the
study groups, were intended to bring the defini-
tions of end points into alignment with clinical
event definitions that had evolved during the
course of the study. Details of the changes in
end-point definitions are provided in Table S1 in
the Supplementary Appendix.
Statistical Analysis
We originally calculated that 1080 participants
would need to be enrolled for the study to have
90% power to test the hypothesis that stenting
would reduce the incidence of the primary end
point by 25% (hazard ratio, 0.75) at 2 years, at a

5322 Potential participants were screened

4375 Were not enrolled

801 Declined to participate
210 Were withdrawn by physician
1866 Met anatomical exclusion criteria
628 Met clinical exclusion criteria
870 Had other unspecified reasons

947 Underwent randomization

467 Were assigned to stent plus medical
therapy
442 Underwent assigned intervention
25 Did not undergo assigned
intervention
9 Did not have stent procedure
attempted
3 Could not have stent delivered
13 Did not meet lesion criteria
480 Were assigned to medical therapy
alone
478 Underwent assigned intervention
2 Declined medical therapy
19 Crossed over to stent plus medical
therapy
7 Reached primary end point
before crossover to stent

8 Were excluded owing to 8 Were excluded owing to

scientific integrity issue scientific integrity issue

62 Discontinued follow-up 81 Discontinued follow-up

33 Withdrew before a primary end point
8 Withdrew after a primary end point
19 Were lost to follow-up before a
primary end point
2 Were lost to follow-up after a
primary end point
53 Withdrew before a primary end point
7 Withdrew after a primary end point
18 Were lost to follow-up before a
primary end point
3 Were lost to follow-up after a
primary end point

459 Were included in primary analysis 472 Were included in primary analysis

Figure 1. Screening, Randomization, and Follow-up.

All the participants who underwent randomization were included in the primary analysis, with the exception of the
16 participants (8 in each group) enrolled at a single site at which concerns regarding scientific integrity related to
informed consent and eligibility of enrolled participants were raised during monitoring. The 19 patients who
crossed over from medical therapy alone to stent plus medical therapy were included in the intention-to-treat analy-
sis in the medical therapyalone group.

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 Stenting and Medical Ther apy for Renal-Artery Stenosis

two-sided type I error rate of 0.05. Because the Table 1. Baseline Characteristics of the Study Population, According to
recruitment was slower than anticipated, the data Treatment Group.*
and safety monitoring board recommended termi-
nation of recruitment on January 30, 2010 (at which Stenting plus Medical
Medical Therapy Therapy Only
point 947 participants had undergone randomiza- Characteristic (N=459) (N=472)
tion), and follow-up was extended through Septem-
Age (yr) 69.39.4 69.09.0
ber 28, 2012, to preserve the statistical power.
All the analyses were performed on an inten- Male sex (%) 51.0 48.9
tion-to-treat basis. All participants who under- Race (%)
went randomization were included in the inten- Black 7.0 7.0
tion-to-treat analyses with the exception of the Other 93.0 93.0
16 participants (8 in each group) who were en- Body-mass index 28.25.3 28.75.7
rolled at a single site at which scientific integrity
Systolic blood pressure (mm Hg) 149.923.2 150.423.0
issues were identified; an administrative deci-
sion was made to exclude the data from these Blood pressure at target level (%) 29.2 25.3
participants from the intention-to-treat analysis Estimated GFR (ml/min/1.73 m2) 58.023.4 57.421.7
(see additional information below). Continuous Stage 3 chronic kidney disease (%) 49.6 50.4
variables are expressed as means and standard Method of identification of stenosis (%)
deviations and were compared with the use of
Angiography 68.4 68.6
Students t-tests. Medians are presented with in-
Duplex ultrasonography 25.5 24.2
terquartile ranges. Categorical variables are ex-
pressed as proportions and were compared with Computed tomographic angiography 4.4 5.3
the use of the chi-square test or Fishers exact Magnetic resonance angiography 1.7 1.9
test, as appropriate. Time-to-event outcomes Medical history and risk factors (%)
(including the primary end point) are expressed Diabetes 32.4 34.3
as KaplanMeier estimates and were compared
Prior myocardial infarction 26.5 30.2
between the treatment groups with the use of
History of heart failure 12.0 15.1
the log-rank statistic. The Cox proportional-
hazards model was used to estimate the hazard Smoking in past yr 28.0 32.2
ratios and associated 95% confidence intervals. Hyperlipidemia 89.4 90.0
Prespecified secondary analyses included tests Angiographic findings
for interaction effects between the primary end % Stenosis, as assessed by core laboratory 67.311.4 66.911.9
point and sex, race, presence or absence of dia-
% Stenosis, as assessed by investigator 72.514.6 74.313.1
betes, and presence or absence of global renal
ischemia (defined as stenosis of 60% or more of Global ischemia (%)** 20.0 16.2
the diameter of all arteries supplying both kid- Bilateral disease (%) 22.0 18.1
neys or stenosis of 60% or more of the diameter
* Plusminus values are means SD. There were no significant differences be-
of all arteries supplying a single functioning tween the groups in any of the characteristics listed here (P>0.05).
kidney). The effect of treatment on systolic blood Race was self-reported. Other included white (91.5% in the stent group and
pressure over time was estimated with the use of 90.9% in the medical therapyonly group), as well as American Indian or
Alaska Native, Asian, and Native Hawaiian or other Pacific Islander.
a repeated-measures analysis. The body-mass index is the weight in kilograms divided by the square of the
The primary composite end point was tested height in meters.
at the 0.0497 level to adjust for a single interim The target level of blood pressure was less than 140/90 mm Hg for patients
without coexisting conditions and less than 130/80 mm Hg for patients with
analysis. All other analyses were performed at diabetes or chronic kidney disease.
the 0.05 level without adjustment for multiple The estimated glomerular filtration rate (GFR) was calculated with the use
comparisons. of the modified Modification of Diet in Renal Disease formula.
Angiographic data are shown for patients who underwent invasive angiogra-
phy.
** Global ischemia was defined as stenosis of 60% or more of the diameter of
R e sult s all arteries supplying both kidneys or stenosis of 60% or more of the diame-
ter of all arteries supplying a single functioning kidney.
Study Population and Treatment Bilateral disease was defined as stenosis of 60% or more of the diameter of
Between May 16, 2005, and January 30, 2010, a at least one artery supplying each kidney.
total of 5322 patients were screened, and 947

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 2. Clinical End Points.*

Stenting plus Medical Therapy

Medical Therapy Only Hazard Ratio
End Point (N=459) (N=472) (95% CI) P Value

no. (%)
Primary end point: death from cardiovascular or renal causes, stroke, myo- 161 (35.1) 169 (35.8) 0.94 (0.761.17) 0.58
cardial infarction, hospitalization for congestive heart failure, progres-
sive renal insufficiency, or permanent renal-replacement therapy
Components of primary end point
Death from cardiovascular or renal causes 20 (4.4) 20 (4.2)
Stroke 12 (2.6) 16 (3.4)
Myocardial infarction 30 (6.5) 27 (5.7)
Hospitalization for congestive heart failure 27 (5.9) 26 (5.5)
Progressive renal insufficiency 68 (14.8) 77 (16.3)
Permanent renal-replacement therapy 4 (0.9) 3 (0.6)
Secondary clinical end points
Death from any cause 63 (13.7) 76 (16.1) 0.80 (0.581.12) 0.20
Death from cardiovascular causes 41 (8.9) 45 (9.5) 0.89 (0.581.36) 0.60
Death from renal causes 2 (0.4) 1 (0.2) 1.89 (0.1720.85) 0.60
Stroke 16 (3.5) 23 (4.9) 0.68 (0.361.28) 0.23
Myocardial infarction 40 (8.7) 37 (7.8) 1.09 (0.701.71) 0.70
Hospitalization for congestive heart failure 39 (8.5) 39 (8.3) 1.00 (0.641.56) 0.99
Progressive renal insufficiency 77 (16.8) 89 (18.9) 0.86 (0.641.17) 0.34
Permanent renal-replacement therapy 16 (3.5) 8 (1.7) 1.98 (0.854.62) 0.11

* The hazard ratios were calculated with the use of multivariable proportional-hazards regression. P values were calculated with the use of the
log-rank statistic.
Only the first event per participant is included in the composite.
Components of the composite are included only if it was the first event contributing to the primary end point.
The first event for each component of the primary composite end point is included as a secondary end point.

were randomly assigned to stenting plus medical
therapy (467 patients) or medical therapy alone
(480 patients) (Fig.1). The reasons for nonenroll-
ment of screened patients are shown in Figure1
and in Table S2 in the Supplementary Appendix.
One center was found during monitoring to have
obtained consent from some participants after
study procedures were initiated. That site was
terminated from the study, and the 16 partici-
pants at that site were withdrawn from the study,
owing to issues of scientific integrity relating to
informed consent and the eligibility of partici-
pants. All study data are reported for the remain-
ing 931 trial participants.
The two groups were well matched at baseline
(Table1). Among the 472 patients in the medi-
cal-therapy group, 19 crossed over to stenting. A
total of 12 crossovers were not approved by the
crossover committee; 7 were approved because
they occurred after the patients had had a pri-
mary end-point event. Participants were followed
for a median of 43 months (interquartile range,
31 to 55).
Stenting and Periprocedural Events
Stents were placed in 434 of the 459 patients in
the stent group (94.6%) and resulted in a mean
(SD) reduction of the stenosis from 6811% to
168% (P<0.001) (Fig.1). The most common
angiographic complication was arterial dissec-
tion, which occurred in 11 patients (details of
stent treatment, including procedural complica-
tions, are provided in Table S3 in the Supplemen-
tary Appendix). No one in the stent group (or in
the medical therapyonly group) required dialysis
within 30 days after randomization. One person

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 Stenting and Medical Ther apy for Renal-Artery Stenosis

(0.2%) in the stent group initiated dialysis between

30 and 90 days after randomization. A patient 100
randomly assigned to medical therapy alone had 90
a fatal stroke on the day of randomization. 80 Stent plus medical therapy

Event-free Survival (%)

70
Clinical Outcomes 60

There was no significant difference in the occur- 50 Medical therapy alone

rence of the primary composite end point be-
tween the stent group and medical therapyonly
group (35.1% and 35.8%, respectively; hazard
ratio, 0.94; 95% confidence interval [CI], 0.76 to
1.17; P=0.58) (Table2 and Fig.2). In addition,
no significant between-group differences were
observed in the rates of the components of the
primary end point (Table2, and Fig. S1 through
S6 in the Supplementary Appendix). We also
observed no significant difference in all-cause
mortality during the follow-up period (Table2).
No interactions were observed between treat-
ment and the four prespecified subgroups
those defined according to sex, race (black vs.
others), presence or absence of global ischemia,
and presence or absence of diabetes with re-
spect to the occurrence of a primary end-point
event (Fig.3). In addition, no significant differ-
ences in the treatment effect were observed in
other subgroups.
Blood Pressure over Time
At baseline, participants were taking a mean of
2.11.6 antihypertensive medications. At the end
of the study, the number of medications in-
creased in both the stent group and the medical
therapyonly group but did not differ signifi-
cantly between the two groups (3.31.5 and
3.51.4 medications, respectively; P=0.24). Sys-
tolic blood pressure declined in both the medical
therapyonly group (by 15.625.8 mm Hg) and
the stent group (by 16.621.2 mm Hg). In the
longitudinal analysis, the systolic blood pressure
was modestly lower in the stent group than in
the medical therapyonly group (2.3 mm Hg;
95% CI, 4.4 to 0.2 mm Hg; P=0.03), and the
difference persisted throughout the follow-up
period (Fig. S7 in the Supplementary Appendix).
Discussion
The CORAL trial was designed to test whether
renal-artery stenting, when added to protocol-
driven contemporary medical therapy, improves
clinical outcomes in persons with atherosclerotic
40
30
Hazard ratio with stenting, 0.94 (95% CI, 0.761.17)
20
P=0.58 by log-rank test
10
0
0 1 2 3 4 5
Years from Enrollment
No. at Risk
Medical therapy 472 371 314 214 115 40
alone
Stent plus medi- 459 362 318 224 131 59
cal therapy
Figure 2. KaplanMeier Curves for the Primary Outcome.
Survival curves are truncated at 5 years owing to instability of the curves
because few participants remained in the study after 5 years.
renal-artery stenosis. We found no benefit of
stenting with respect to the rate of the composite
primary end point or any of its individual com-
ponents, including death from cardiovascular or
renal causes, stroke, myocardial infarction, con-
gestive heart failure, progressive renal insufficien-
cy, and the need for renal-replacement therapy.
This result was consistent across all prespecified
subgroups, including patients with global renal
ischemia and patients with other high-risk char-
acteristics. We did observe a modest, but statisti-
cally significant, reduction of 2 mm Hg in systolic
blood pressure with stenting, but this reduction
did not translate into a reduction in clinical events.
Other randomized trials, including the An-
gioplasty and Stenting for Renal Artery Lesions
(ASTRAL) trial15 and the Stent Placement and
Blood Pressure and Lipid-Lowering for the Pre-
vention of Progression of Renal Dysfunction
Caused by Atherosclerotic Ostial Stenosis of the
Renal Artery (STAR) trial,16 assessed the useful-
ness of renal-artery stenting with respect to
kidney function and showed no significant dif-
ference in this key measure. These studies have
been criticized for enrolling some participants
who did not have clinically significant renal-artery
stenosis and for not having their findings con-
firmed by core laboratories.21 In addition, none
of the previous studies were designed specifi-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Stent plus Medical Medical Therapy P Value for

Subgroup Therapy Alone Hazard Ratio (95% CI) Interaction
no. of patients/total no. (%)
Overall 161/459 (35.1) 169/472 (35.8) 0.94 (0.761.17)
Creatinine level 0.09
>1.6 mg/dl 43/84 (51.2) 34/87 (39.1) 1.35 (0.862.11)
1.6 mg/dl 112/352 (31.8) 128/367 (34.9) 0.87 (0.671.12)
Estimated GFR 0.80
45 ml/min/1.73 m2 91/288 (31.6) 105/311 (33.8) 0.93 (0.701.23)
<45 ml/min/1.73 m2 64/148 (43.2) 57/143 (39.9) 0.98 (0.681.40)
Diabetes 0.17
Yes 69/148 (46.6) 66/162 (40.7) 1.15 (0.821.61)
No 92/309 (29.8) 103/310 (33.2) 0.84 (0.641.12)
Sex 0.64
Male 75/234 (32.1) 78/231 (33.8) 0.89 (0.651.22)
Female 86/225 (38.2) 91/241 (37.8) 0.99 (0.741.33)
Global ischemia 0.32
Yes 39/89 (43.8) 20/51 (39.2) 1.07 (0.621.83)
No 119/356 (33.4) 106/264 (40.2) 0.78 (0.601.01)
Race 0.62
Black 11/29 (37.9) 10/30 (33.3) 1.01 (0.422.43)
Other 126/356 (35.4) 136/357 (38.1) 0.88 (0.691.13)
Baseline systolic blood pressure 0.55
>160 mm Hg 66/148 (44.6) 58/139 (41.7) 1.02 (0.711.45)
160 mm Hg 95/309 (30.7) 108/328 (32.9) 0.90 (0.681.18)
Age 0.56
>70 yr 91/226 (40.3) 94/220 (42.7) 0.87 (0.651.16)
70 yr 70/233 (30.0) 75/252 (29.8) 1.00 (0.721.39)
U.S. sites 0.38
Yes 137/385 (35.6) 146/387 (37.7) 0.90 (0.711.14)
No 24/74 (32.4) 23/85 (27.1) 1.22 (0.692.16)
Maximal diameter stenosis 0.66
80% 77/198 (38.9) 64/166 (38.6) 0.93 (0.671.30)
<80% 77/231 (33.3) 79/208 (38.0) 0.84 (0.611.14)
0.4 0.6 1.0 1.6 2.7

Stent plus Medical

Medical Therapy
Therapy Better Alone Better

Figure 3. Forest Plot of Treatment Effects within Subgroups.

Hazard ratios for stenting plus medical therapy versus medical therapy alone include all available follow-up data for the primary com-
posite end point. None of the tests for treatment and subgroup interaction were significant (P>0.05). To convert the values for creati-
nine to micromoles per liter, multiply by 88.4. The estimated glomerular filtration rate (GFR) was calculated with the use of the modified
Modification of Diet in Renal Disease formula. Global ischemia was defined as stenosis of 60% or more of the diameter of all arteries
supplying both kidneys or stenosis of 60% or more of the diameter of all arteries supplying a single functioning kidney. For the sub-
group of blacks versus others, the analysis was limited to U.S. sites. SBP denotes systolic blood pressure.

cally to detect a benefit with respect to clinical
events. We sought to address these concerns in
CORAL.
A key issue in the interpretation of our results
is whether the medical therapy that was given to
CORAL participants can be replicated in clinical
practice. The medical therapy in our study in-
cluded the use of an angiotensin-receptor block-
er, with or without a thiazide-type diuretic, with
the addition of amlodipine for blood-pressure
control. In addition, participants received anti-
platelet therapy and atorvastatin for management
of lipid levels, and diabetes was managed ac-
cording to clinical practice guidelines.19,20 With
this regimen, patients who received medical treat-
ment alone had remarkably good cardiovascular
and renal outcomes, despite their advanced age
and the high rates of hypertension, diabetes,

20 n engl j med 370;1nejm.org January 2, 2014

The New England Journal of Medicine

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 Stenting and Medical Ther apy for Renal-Artery Stenosis

chronic kidney disease, and other coexisting car-
diovascular conditions.
Renal-artery stenting remains a common pro-
cedure in current clinical practice. The CORAL
study shows that, when added to a background
of high-quality medical therapy, contemporary
renal-artery stenting provides no incremental
benefit. From this result, it is clear that medical
therapy without stenting is the preferred man-
agement strategy for the majority of people with
atherosclerotic renal-artery stenosis.
The CORAL trial had some limitations. First,
patients could be enrolled in the trial with renal-
artery stenosis of 60% or more, and there is debate
about the severity of stenosis that is necessary to
justify intervention.22 However, we were unable
to show a benefit among participants with renal-
artery stenosis of more than 80%, as measured
by the enrolling investigators. Second, we did not
include patients with fibromuscular dysplasia, and
several studies suggest that angioplasty alone may
improve blood-pressure control and even cure
hypertension in young persons.23 Third, al-
though the inclusion criteria for CORAL were
intentionally broad, some patients who were
screened and deemed to be eligible were not
enrolled in the trial, including patients who
were not enrolled because of the preference of
their physician. Some of these patients may have
been treated by means of stenting by physicians
who were convinced of the clinical benefit of
the procedure. Nonetheless, the baseline clinical
and angiographic characteristics of the study
population, as well as the response with respect
to systolic blood pressure, were remarkably simi-
lar to those in patients enrolled in previous single-
group, FDA-approval trials of renal stents.24-26
In summary, renal-artery stenting did not
confer a significant benefit with respect to the
prevention of clinical events when added to com-
prehensive, multifactorial medical therapy in
people with atherosclerotic renal-artery stenosis
and hypertension or chronic kidney disease.
The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
Supported by grants (U01HL071556, U01HL072734,
U01HL072735, U01HL072736, and U01HL072737) from the Na-
tional Heart, Lung, and Blood Institute of the National Insti-
tutes of Health.
Dr. Murphy reports holding equity interest in Summa Thera-
peutics. Dr. Cutlip reports that his institution holds research
contracts with Medtronic, Boston Scientific, and Abbott Vascu-
lar. Dr. Cohen reports receiving personal fees from Abbott, As-
traZeneca, Eli Lilly, and Medtronic, and grant support from Ab-
bott, AstraZeneca, Eli Lilly, Medtronic, Boston Scientific,
Biomet, and Janssen. Dr. Matsumoto reports receiving consult-
ing fees from Boston Scientific and the Medicines Company and
grant support from Medtronic, Cook and W.L. Gore. Dr. Jaff re-
ports receiving consulting fees from AstraZeneca and serving as
an uncompensated advisor to Cordis, Boston Scientific, Abbott,
Covidien, and Medtronic. Dr. Lewis reports receiving grant sup-
port from Novartis, Amgen, and Sanofi Aventis. Dr. Tuttle re-
ports receiving consulting fees and grant support from Eli Lilly.
Dr. Rundback reports receiving fees for board membership from
VIVA Physicians, personal fees from Covidien, Biotronik, and St.
Jude, and lecture fees from Covidien and CSI. No other potential
conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.

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